Metabolic fate of zetidoline,a new neuroleptic agent,in man

Summary Healthy volunteers administered orally a single dose (20 mg) of [2-¹⁴C]zetidoline, a new dopamine antagonist, exhibited rapid absorption of radioactivity with peak plasma levels of 250–300 ng/ml achieved in 1 h. The compound underwent intensive metabolic first-pass so that plasma radioactivity was represented mostly by two products, metabolite B endowed with neuroleptic activity, and metabolite D inactive, while unchanged zetidoline was not detected. Disappearance of radioactivity from plasma was rapid with a half-life of 1.78±0.20 h.The simultaneous assay of plasma prolactin showed increased levels of the hormone (+464% at the peak time) up to the 6th h after dosing, with plasma concentration profile which mimic those of metabolite B.The radioactive test-dose was eliminated mainly via the kidneys with an average urinary recovery of 84.7±1.7% in 4 days (73.4±1.1% within 8 h). The main urinary metabolite (metabolite G) and two minor ones (metabolites B and D) were purified and their structures assigned by IR, MS and NMR spectroscopy, they are: 1-(3-chloro-4-hydroxyphenyl)-3[2-(3,3-dimethyl-1-azetidinyl)ethyl]imidazolidin-2-one, metabolite B; 1-[2-(3,3-dimethyl-1-azetidinyl)ethyl]imidazolidin-2-one, metabolite D and the 4-O-sulphate ester of metabolite B, metabolite G.The metabolic fate of zetidoline in man follows the same phase I reactions demonstrated in rats and dogs, while the phase II reaction is sulphoconjugation instead of the glucuronidation observed in animals.     

In vitro Metabolism of Bumetanide

A new metabolite of the diuretic drug bumetanide, the 4-[(4-hydroxy)-phenoxy] analog (7), was identified in incubation mixtures of rat liver microsomes. Phenobarbital and clofibrate pretreatment to induce microsomal enzymes changed the relative amounts of the six metabolites formed. Compound 7was the most prevalent metabolite after clofibrate pretreatment.     

Sarcopenia and Appendicular Muscle Mass as Predictors of Impaired Fasting Glucose/Type 2 Diabetes in Elderly Women

Elderly women exhibit a high risk of type 2 diabetes (T2D), but no definitive data exist about the possible role of postmenopausal increases in visceral adiposity, the loss of lean body mass, or decreases in the sum of the lean mass of arms and legs (appendicular skeletal muscle mass (ASMM)). This retrospective, longitudinal study investigated whether body composition (bioelectrical impedance analysis) predicted the development of impaired fasting glucose (IFG) or T2D in a cohort of 159 elderly women (age: 71 ± 5 years, follow-up: 94 months) from southern Italy (Clinical Nutrition and Geriatric Units of the “Mater Domini” University Hospital in Catanzaro, Calabria region, and the “P. Giaccone ”University Hospital in Palermo, Sicily region). Sarcopenia was defined in a subgroup of 128 women according to the EWGSOP criteria as the presence of low muscle strength (handgrip strength <16 kg) plus low muscle mass (reported as appendicular skeletal muscle mass <15 kg). Participants with a low ASMM had a higher IFG/T2D incidence than those with a normal ASMM (17% vs. 6%, p-adjusted = 0.044); this finding was independent of BMI, fat mass, waist circumference, and habitual fat intake (OR = 3.81, p = 0.034). A higher incidence of IFG/T2D was observed in the subgroup with sarcopenia than those without sarcopenia (33% vs. 7%, p-adjusted = 0.005) independent of BMI and fat mass (OR = 6.75, p = 0.007). In conclusion, this study demonstrates that elderly women with low ASMM had a higher probability of developing IFG/T2D. Further studies are needed to confirm these results in men and in other age groups.     

Intracranial capillary hemangiomas: literature review in pediatric and adult population

Neurosurgical Review - Capillary hemangiomas (CHs) of the central nervous system represent a rare diagnosed pathology. CHs are benign vascular tumors whose most common manifestations are dermal and...     

Conversion of Fused Hip to Total Hip Arthroplasty: Long-Term Clinical and Radiological Outcomes

BackgroundDespite promising results at the mid-term followup, several aspects of conversion of the fused hip to total hip arthroplasty (THA) remain controversial. The aim of this study was to evaluate clinical and radiological outcomes with a minimum 5-year followup in patients who underwent conversion of the fused hip to THA.MethodsFifty-seven patients (59 hips) were evaluated. The Harris Hip Score (HHS), range of motion (ROM), and the Visual Analogue Scale (VAS) were used to assess hip function and low back pain. Subjective satisfaction with surgery and the presence of the Trendelenburg sign was also evaluated. Radiological assessment was performed pre- and postoperatively to evaluate loosening and heterotopic ossification (HO).ResultsAfter a mean followup of 13.0 ± 6.2 years, HHS and VAS significantly improved from 46.0 ± 16.7 to 80.8 ± 18.8 and from 4.4 ± 1.5 to 2.1 ± 1.4 (both P < .001), respectively. Twenty-three patients (40.4%) had a positive Trendelenburg sign, and HOs were found in 29 cases (49.1%). An overall 29.8% complication rate was noted. Smoking habits and rheumatoid arthritis were predictive of Trendelenburg sign (P = .046 and P = .038, respectively). Implant survival rate as the end point was 98.7 ± 1.3% at 5 years, 92.4 ± 3.3% at 10 years, 82.1 ± 5.7% at 15 years, and 73.4 ± 8.0% at 20 and 25 years. A worse cumulative implant survival rate was noted in patients who underwent previous hip surgery, defined as any hip operation before fusion (P = .005).ConclusionConversion of the fused hip to hip arthroplasty provides high levels of hip functionality and satisfaction with surgery at long-term followup. An implant survival rate higher than 70% can be expected 25 years postoperatively.     

Modified full-face snorkeling mask for thoracic surgery and otolaryngology surgical use: comfort and usability assessment during the COVID-19 pandemic

Background:A worldwide personal protection equipment (PPE) shortage has emerged during COVID-19 pandemic, contributing to the high incidence of SARS-CoV-2 infection among health care providers. To address this lack of PEE, new solutions have been researched. Among those, full-face snorkeling masks demonstrated to be an interesting option. Among surgical specialties otolaryngologists and thoracic surgeons are at high risk of infection, due to the close contact with airway secretions.Objectives:We tested the comfort and usability of a modified full-face snorkeling mask (Ocean Reef Mask Aria QR+) as a protective device for otolaryngologic and thoracic surgeries.Methods:The mask was customized with a 3D-printed adaptor supporting many industrial filter types, including FFP3 and heat and moisture exchangers (HME). We evaluated surgical performances of the mask, both subjectively, with a questionnaire filled in by the surgeons, as well as objectively, monitoring transcutaneous PCO₂ and PO₂ values of surgeons during surgical procedures.Results:The modified full-face snorkeling mask was tested during 9 otolaryngologic and 15 thoracic surgery procedures. The device demonstrated very good overall vision quality with some limitations regarding lateral vision and almost no difficulties in usability. Water condensation into the mask was absent in almost every case. Both PO₂ and PCO₂ parameters remained within normal ranges during every procedure.Discussion:The modified full-face snorkeling mask can be an innovative PPE. In the current COVID-19 pandemic scenario, the worldwide shortage of protective masks and goggles may exploit this ready-to-use and low-cost solution, especially for high-risk surgical procedures.     

Hydrophobic Bombyx mori Silk Fibroin: Routes to Functionalization with Alkyl Chains

Bombyx mori silk fibroin (SF) is a very versatile biopolymer due to its biocompatibility and exceptional mechanical properties which make possible its use as a functional material in several applications. SF can be modified with a large variety of chemical approaches which endow the material with tailored chemical–physical properties. Here, a systematic investigation of different routes is reported to graft long alkyl chains on SF based on both liquid- and solid-phase, aiming to modulate its hydrophobic behavior. The liquid phase method involves direct activation of SF tyrosine residues via diazo coupling and cycloaddition reactions, generating hydrophobic materials insoluble in any common solvent. The solid phase approach consists of the chemical modification of drop-casted SF films by esterification of hydroxyl groups of serine, threonine, and tyrosine SF residues with acyl chlorides of fatty acids. For the solid-state functionalization, a new class of hydrophobic pendant groups is synthesized, based on triple esters of gallic acid anhydrides, that are reacted with the biopolymer to further enhance its resulting hydrophobic features.     

Immunohistochemical detection of p140trkA and p75LNGFR neurotrophin receptors in neuroblastoma

In neuroblastoma, high levels of mRNA for p14h ^trkA and p75 ^LNGFR neurotrophin receptors are predictive of favorable outcome. Their evaluation by Northern blot, however, requires substantial amounts of tissue and this prevents their routine evaluation as well as the possibility for multicenter studies to be easily carried out. In an attempt to overcome these limitations, the feasibility and reliability of determining both neurotrophin receptors on cryostat sections by immunohistochemistry were assessed, and these findings were compared to those obtained from Northern blot analysis. Primary tumor samples from 28 untreated patients at all stages were evaluated by using H10 anti-p140 ^trkA and ME20.4 anti-p75 ^LNGFR mAbs. Although weak, positiveimmunostaining was found in 9 of 28 tumors for p140 ^trkA and in 5 of 28 tumors for p75 ^LNGFR . As compared to Northern blot, the concordance rate was 79% (22 of 28 cases) for p140 ^trkA (p < 0.05) and 71% (20 of 28 cases) for p75 ^LNGFR (p < 0.05). No case negative for Northern blot was found to be positive with immunohistochemistry. Since only high mRNA levels for both receptors have been shown to be clinically relevant, their immunohistochemical detection, although less sensitive than Northern blot, can be just as sufficient and reliable as a prognostic tool, and possibly with a better cost-benefit ratio.